1. Field of the Invention
The invention relates to novel amides of L-aspartyl-D-serine and L-aspartyl-D-O-methylserine which are especially useful in view of their potent sweetening properties, novel methods for their use in foods and edible composition containing them.
2. Description of the Prior Art
In U.S. Pat. No. 3,492,131 certain lower alkyl esters of L-aspartyl-L-phenylalanine were found to be up to 200 times as sweet as sucrose and to be substantially free of bitter flavor notes which detracted from earlier artificial sweeteners such as saccharin. These compounds were subsequently found to have only limited stability in aqueous systems due to diketopiperazine formation especially at the neutral-acidic pH conditions prevalent in most food systems.
Mazur et al., J. Med. Chem., 16, 1284 (1973) has disclosed that lower alkyl esters of L-aspartyl-D-alanine and certain homologs thereof, especially L-aspartyl-D-alanine isopropyl ester, have sweetness potencies of up to 125 times sucrose.
Sukehiro et al., Seikatsu Kagaku, 11, 9-16 (1977); Chem. Abstr., 87, 168407h (1977) has disclosed certain amides of L-aspartyl-D-alanine of the formula ##STR3## where R.sup.1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, secondary butyl, cyclohexyl or the carbon residue of the methyl esters of glycine, d-alanine or l-alanine. The most potent compounds were those wherein R.sup.1 is one of the above butyl groups or cyclohexyl, having respectively, 100-124 and 100 times the sweetness of sucrose. Since the n-butylamide was found to have 125 times the sweetness of sucrose and the isobutyl and secondary butyl amides are 100x sucrose, it was concluded that the potency of these amides is affected mainly by the number of carbon atoms in the alkyl group, R.sup.1, and that structural isomerism in the alkyl group has little effect on the sweetness potency.
Esters of L-aspartyl-D-serine and L-aspartyl-D-threonine have been found by Ariyoshi et al., Bull. Chem. Soc. Japan, 47, 326 (1974) to be sweeter than the corresponding esters of L-aspartyl-D-alanine and L-aspartyl-D-2-aminobutyric acid, respectively. The most potent of these esters, L-aspartyl-D-serine n-propyl ester, was 320 times as sweet as a 5% sucrose standard.
U.S. Pat. No. 3,971,822 discloses esters of L-aspartyl-D-alaninol with carboxylic acids, including 2-methyl-butyric, cyclopropane carboxylic, cyclobutanecarboxylic and 2- methylcyclobutanecarboxylic acids. The esters with cyclopropane- and cyclobutanecarboxylic acids were 200 x and 220 x sucrose, respectively. The ester with 2-methylcyclobutanecarboxylic acid was only 160 x sucrose. Corresponding L-aspartyl-D-serinol esters are also disclosed, the sweetest of which, the ester with propionic acid, is 160 x sucrose.
U.S. Pat. Nos. 3,959,245 and 3,907,766 disclose, respectively, L-aspartylaminomalonic acid methyl 2-methylcyclohexyl diester, and the corresponding alkyl fenchyl diester. The former is reported to be 6600 x sucrose, the latter 4200-33,000 x sucrose. In a related publication by the inventors, Chem. Pharm. Bull., 24, 2112 (1976), a series of L-aspartylaminomalonic acid diesters is disclosed, one of the ester groups being methyl or ethyl and the other being one of a variety of branched alkyl and cycloalkyl groups.